Time is the overarching topic of this lecture, and to illustrate its amazing dimensions, Ahmed Zewail begins his talk by showing the transparency with which he had concluded his Nobel lecture two and a half years before.[1] It displays a time scale that spans more than thirty orders of magnitude, from the big bang to the motion of atoms in the femto- to attosecond range, with the human heartbeat exactly in the middle between the two limits. “There is an incredible symmetry”, says Zewail whose invention of laser-based femtosecond spectroscopy has made it possible to observe molecular interactions in “slow motion”. A femtosecond relates to a second as a second relates to 32 million years!

Yet according to the rules of quantum theory, the motion of atoms would be impossible to detect, Zewail says. “If you deal with an experiment that is averaging over time, you would not see any motion - you’d just see a probability over all distances”. By shortening time resolution down to the femtosecond range, however, one can “transform a quantum system with a probability over all nuclear distances into a system, which is localized in space” so that one “can speak now almost classically of a system moving x Angstrom in y femtoseconds”. But this is still not sufficient, because there is “an obstacle called the uncertainty principle”, which states that if time is very short it is impossible to narrowly confine energy or frequency, respectively. Therefore one has to conduct such experiments with coherent laser light. In a coherent beam, the uncertainty principle can be neglected because specific molecules are not of interest. Each of them remains anonymous and needs not to be accurately tracked.[2] “The bottom line is very simple to understand”, says Zewail. “We convert a discrete system almost into a continuous system coherently and therefore - even though we are dealing with a quantum system -we are at a classical limit where we can define now a velocity for the atom and a trajectory in space and time.”

With an “example that JD Bernal has reflected on”, namely the “regular formation of ice” during the hydration of proteins, Zewail presents “the essence of one biological application” of femtosecond spectroscopy in the second third of his lecture. He explains how one can switch on a dipole in the indole group of tryptophan within femtoseconds and then observe how the water molecules solvate these dipoles. „Following the femtosecond switching of the dipole we get something like the hydration-correlation function and all the time components that are necessarily involved in this dynamical picture.“ Observing the hydration dynamics of tryptophan as a part of large proteins rather than as a single molecule reveals insights about important surface mechanisms during the process of protein folding and may also be „shining some light in a double meaning on the mechanisms by which proteins are recognizing each other“.

In the last third of his lecture, Zewail sketches a research area that currently is of fundamental interest to him: „We want to use electrons to be able to get ultimately the molecular structure all at once“, he says. He aims at tuning femtosecond electron pulses in specific intermediates and gathering from the diffraction data how the system is evolving as a function of time. Confidently he reports on very recent data from an aromatic molecule, which is just opening its ring.

[2] Here, Zewail explicitly refers to laser pioneer Charles Townes, who recalled the initial objections of great phycisists like Bohr and Rabi against the maser in his book „How the laser happened“: „A corollary, on which the maser’s doubters stumbled, is that one cannot measure an object’s frequency (or energy) to great accuracy in an arbitrarily short time. Measurements made over a finite time automatically impose uncertainty on the frequency. To many phycisists steeped in the uncertainty principle, the maser’s performance, at first blush, made no sense at all. Molecules spend so little time in the cavity of a maser…that it seemed impossible for the frequency to be also narrowly confined. …There is good reason, of course, that the uncertainty principle does not apply so simply here. The maser does not inform one about the energy of frequency of any specific …molecule…Each individual molecule remains anonymous, not accurately measured or tracked…” (p.70)

Abstract

In this lecture we will highlight some of the recent advances in using Ultrafast Electron Diffraction to study transcient structures and with femtosecond resolution the biological dynamics of proteins and DNA.